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Hidden
genetic
variation
From recognition to acknowledgement
of genetic individuality
Prof.dr J.E. Kammenga
Inaugural lecture upon taking up the position of Personal Professor of
Functional genetics at the laboratory of Nematology
at Wageningen University & Research on 8 December 2016
Hidden genetic variation
From recognition to acknowledgement
of genetic individuality
Prof.dr J.E. Kammenga
Inaugural lecture upon taking up the position of Personal Professor of
Functional genetics at the laboratory of Nematology
at Wageningen University & Research on
8 December 2016
doi http://dx.doi.org/10.18174/409705
isbn 978-94-6343-135-4
Hidden genetic variation
From recognition to acknowledgement
of genetic individuality
Introduction
Esteemed Rector Magnificus, colleagues, family, friends and students,
Today I will outline and explain the problem of understanding genetic individuality
and hidden genetic variation as part of my vision on research. Next to this I will give
my view on the attitude of today’s students with respect to their study and the need
to foster new relationships with immigrant pupils.
Characteristics of individuals are determined by genes, the environment and the
interaction between genes and the environment. Already early at school have we
learned that many traits are determined by single genes, for instance, the eye colour
in fruit flies and the colour of peas. Dominant and recessive forms determine the
effect of these genes. More recent research has shown that the overall appearance and
position of twigs is determined by a single gene in sweet pepper [1]. Such traits are
called monogenic or Mendelian traits, named after Gregor Mendel (1822-1884), the
founding father of genetic research. Contemporary genetics still involves intensive
research based on his ideas and experiments, assuming that many traits are
considered monogenic. A very recent example of a single gene study was published
in the top journal Nature this year. It involved the classic case of genetic adaptation
of the peppered moth to a polluted and black environment caused by industrial
emission in the United Kingdom. A phenomenon called melanism where black
coloured phenotypes are favoured over the light coloured wild type (Figure 1). This
adaptation was found to be determined by a mutation in a single gene caused by a
so-called transposable element (piece of DNA that is inserted into the gene) that
landed in the cortex gene[2], a cell cycle regulator[3].
Wageningen University & Research | 3
Monogenic traits have also been studied extensively in humans, in particular
monogenic rare diseases like cystic fibrosis (disease of the lung)[4], the Miller
syndrome (genetic disorder of facial expression, arms and legs)[5] and specific cases
of mitochondrial diseases caused by mutation in polymerase-γ [6]. Mutation in
polymerase-γ leads to clumps of diseased mitochondria (the machines where energy
is produced) in muscle tissue. Overall, our knowledge about single gene mutations
and their effect on a range of disease traits has tremendously increased over the past
couple of decades. The bigger picture is well known. Currently, more than 5000
genes have been identified where mutations in these genes give rise to approx. 4500
types of disease and disorders (https://www.genetests.org/).
But humans are notoriously difficult to study for ethical and technical reasons.
Experimentally induced mutant screens in model organisms have been powerful for
identifying genes and mutations that underlie phenotypes of interest, including
complex human diseases. These screens involve the induction of DNA mutations
called mutagenesis by exposing model organisms like flies, mice and worms in the
laboratory to mutagens or rely on insertional mutagenesis such as transposable
elements. Subsequently, mutated individuals are isolated by selective breeding for
the phenotypes of interest, after which the gene is mapped and characterized. I now
focus a bit more on the nematode Caenorhabditis elegans that was introduced (actually,
it was taken from a compost heap) as a genetic model in the early seventies by
Sydney Brenner who was interested in the developmental biology of neurons [7]. C.
elegans is 2 mm long and has a rapid life cycle of 2.5 days. Because the worm was
transparent they studied how cells develop into a worm. Together with Jonathan
Sulston and Rob Horvitz did he map out the entire cell lineage (egg to worm)
Figure 1. The black variant of the moth Biston betularia is a genetic adaptation to industrial pollution
due to a mutation in a single gene. https://commons.wikimedia.org/w/index.php?curid=868091
4 | Prof.dr J.E. Kammenga Hidden genetic variation
Figure 2. Dividing cells drawn by J. Sulston. http://www2.mrc-lmb.cam.ac.uk/
achievements/lmb-nobel-prizes/2002-sydney-brenner-bob-horvitz-john-sulston/
of C. elegans. Figure 2 shows the drawings they made. During their endeavors they
discovered the phenomenon of programmed cell death or cell suicide (Figure 2). This
facilitated research into understanding cancer formation in humans. As John Sulston
explained about the unity of life: “...nature is not reinventing but is reusing whole
mechanisms. From worms to humans..” For their discoveries and their work they
received the Nobel prize in 2002. Their research was driven by their pursuit of
understanding neuronal development in a worm. Just for the sake of it because the
worm was so transparent.
At the time Sidney Brenner saw profound research potential in the nematode. He
also was not distracted by questions about relevance to society and potential application. Or questions like: why would you do this? Today, it would be virtually impossible to obtain grants for his type of research. Here I adopt the contrarian view by
taking away the negative flavour that we witness today in the research funding
landscape. There should be more room for building Ivory towers. Yes, perhaps it
should be more possible to have a lab in the ivory tower again which is designated
as an environment of intellectual pursuit disconnected from the practical concerns
of everyday life.
Wageningen University & Research | 5
Genetic individuality
Since the discoveries by Brenner and colleagues all research in C. elegans has been
carried out in a single genetic background. Thousands of mutants have been
generated to study genetic pathways, and to elucidate complex disease pathways
underlying cancer or Alzheimer’s disease. Because many genes and their functions
are conserved across other species, the results generated from these single
backgrounds are often interpreted in a general way as being relevant for humans.
And the same applies to other model organisms.
Evidence is growing that we not fully understand the effect of mutations and that we
are caught by surprise about the complexity of individual plants and animals. I will
address the importance of genetic individuality regarding the effect of mutations and
provide insight into understanding this individual complexity. This will be my first
message. Here, I define genetic individuality as the total of all other genes that
possibly interact with the mutation and that give rise to phenotypic variation. So,
each individual has its own unique genetic background.
Before I continue, I would like to walk you through the next figure (Figure 3). Figure
3A looks like a soccer field. And that is what it is. You see the formation 4-5-1. Now I
do not want to engage into an endless discussion with you about the formation, but
what you need to remember is that the striker, the goal keeper and the wing player
are considered as “key” players. The other members of the team play a different,
background, role but may very well determine the success of the whole team. If you
change these background team members, you will change the characteristic of the
team. Of course this depends on the team itself. In Figure 3B, you see a figure not
resembling a football field. And that is also not what it is. It is a cell, and you can see
different genes. Now I do not want to engage into an endless discussion with you
about the type of cell, but what you need to remember is that the red genes are
considered as “key” players. The other genes play a different, background, role but
may very well determine the success of the cellular functions. If you change these
background genes, you will change the characteristic of cell and the individual. Of
course this depends on the individual.
Mutations and genetic individuality
Genetic individuality plays an important role in the effect of mutations affecting
disease phenotypes. In case of cystic fibrosis (CF) we know that up to half of all CF
patients which carry the homozygous DF508 CFTR mutation (CFTR encodes for a
plasmic membrane in the chloride channel of epithelial cells) [4] display a large
variation in CH clinical symptoms such as differences in infection levels and tissue
damage and repair. This variation is caused by differences in the genetic background
of the individual patients. A strong background effect has been reported for
mutations in polymerase-γ (POLG), a major human disease gene that accounts for
6 | Prof.dr J.E. Kammenga Hidden genetic variation
Figure 3. A. Soccer field depicting red ”key” players. Blue dots are background
players. Together they work as a team but the blue players can enhance or
diminish the effect of the key players. B. Cell with red “key” genes. Blue dots
are background genes. Together they determine phenotypic traits but the blue
genes can enhance or diminish the effect of the key genes.
almost 30% of mitochondrial diseases in the UK and in Italy. Although many patients
are homozygous for this mutation, clinical phenotypes are highly variable. All
patients are epileptic, 80% have other neuropathologies and 60% have eye muscle
disease [8].
The importance of the genetic background has been recognized for a long time. Yet, it
has not been widely acknowledged. It is important to make this distinction because
recognition means that “we know that everybody is different”, whereas
acknowledgement means that “we know how it works”. In medical research as well
as plant and animal breeding the genetic individuality is recognized. Every breeder
of tomatoes can tell you which variants you need to cross in order to obtain a tasty
fruit. And a dog breeder would give you advice on which variant not to cross
because of its aggressive nature. So, genetic individuality has long been recognized
but very few attempts have been made to understand the genetic background effects
in a mechanistic way. This is illustrated in medically oriented research focusing on
human disease pathways in mice. Mice are very important animals that are widely
used to in medical research. A Genetic Background Manual is available from The
Jackson Laboratory, an institute with long standing record in mouse genetics.
The manual describes clear examples where the genetic background has been
Wageningen University & Research | 7
Figure 4. Effect of genetic background on expressivity of a mutation in the gene dad-1 in
Petunia. The mutation leads to a compact phenotype. The homozygous recessive mutation (a
transposon insertion) crossed into variants EasyRider (EzR) en EasyWave (EzW) yields
different phenotypes. The red boxes show the F2 generation for 3 offspring. Data kindly
provided by Georgios Vlachakis, Scienza Biotechnologies.
misleading – that is – confounds the phenotypic effect of a mutation, and explains
how to take this into account (correct for it) in experiments involving mice. So, the
problem of the background is recognized but not acknowledged. In conclusion,
mutant screens do not acknowledge genetic individuality where the genetic
background might overshadow the effect of gene functions, a concept called
“hidden genetic variation”.
Hidden genetic variation: from flowers to cancer
Hidden genetic variation affects many traits in plants, animals and humans. Scientists
from a plant breeding company contacted me recently regarding problems they
encountered with a specific mutation in a gene affecting compactness in Petunia.
Compact plants are easier to store and transport. Figure 4 shows two wild type
variants of Petunia, the ones you can buy at your local nursery. These variants are not
compact; they have a more stake-like appearance if you do not prune them, as shown
on the left hand side of the figure. A mutation in the gene dad-1 (decreased apical
dominance-1) yields a much more compact type of plant[9]. Yet, unexpectedly,
enormous variation has been observed regarding compactness. Every offspring
originating from a cross has a different appearance, and strikingly, these differences
8 | Prof.dr J.E. Kammenga Hidden genetic variation
are also pronounced in a variable way in the two different plant varieties – that is – a
different genetic background. Although this variation could be due to background
mutations which came along with the dad-1 mutation, these differences are seen
across both varieties suggesting a strong background effect. We are now working
with this breeding company to unravel the mechanism of these background effects.
Figure 5 shows an interesting case about the effect of a cancer causing mutation (the
mutation in the adenomatous polyposis coli gene on position R850 ApcR850X/+
(Min) in the intestinal tract of mice. The picture shows thin slices of three parts of the
intestinal tract (duodenum) of a two mice A and B, and a piece of the colon. Here the
phenotypic readout is the number of adenomatous polyps. You can clearly see the
polyps which are bluely stained. Polyps signify a first stage in cancer formation.
Mouse type A has many polyps whereas mouse type B has hardly any. You would
expect the mutant is A and the non-mutant is B. This is not the case. Both strains
carry the mutation. This is a very clear case of hidden genetic variation in cancer
phenotypes where we see the effect of the genetic background on polyp formation
in the mouse.
Figure 5. Effect of genetic background on polyp formation in the digestive tract of mice. Both
strains A and B carry the same mutation in the adenomatous polyposis coli gene. Many polyps
are formed in strain A but not in strain B. Courtesy of F. Iraqi.
Wageningen University & Research | 9
A very recent paper reported on the background effects of a mutation in a gene
known to be associated with type-2 diabetes[10]. Many mouse researchers study
mutations in a strain called B6. But here they crossed the mutation with 30 different
backgrounds and then analysed these for its effect on activity, blood glucose levels
and fear response. It was noted that in case of the other backgrounds, results were
highly different and even opposite to the observed effects in B6.
Over the past few years our understanding of “monogenic” disorders and diseases
has shifted, and it is clear that there is a great deal of variability in the phenotypes
associated with specific “causal” genes. A recent study identified human adults
harbouring mutations for a number of severe Mendelian conditions, but no evidence
of associated disease symptoms[11]. Instead of focusing on causal mutations in
diseased individuals, the authors examined healthy people of disease-causing
mutations. They sequenced the DNA of healthy individuals and looked for
mutations in disease genes. They found people with mutations in disease genes but
had no disease. These people were healthy individuals who buffered the effects of
rare, highly penetrant, deleterious mutations. These findings suggest that incomplete
penetrance disease genes may not be un-common and depends on the so-called
background[12].
What is the mechanism of the background effect
on mutant phenotypes?
The aforementioned cases in flowers and cancer in mice and complex diseases in
humans find their origin in the fact that mutations are implicitly regarded as
independent, isolated cases of gene changes. Thereby assuming that the mutant
phenotype is related on a one-to-one basis with the mutation. But this is quite
misleading. The phenotype is not the result of a mutation but of the mutation in
interaction with the genetic background. This is a fundamentally different concept.
To understand this a bit more we look at two genetic backgrounds in worms, one
from England and one from Hawaii. Colleagues of ours reported that the severity of
a mutation in a gene could be predicted from the expression level variation of the
affected gene [13]. For instance, if a phenotype was determined by three genes with
equal expression levels, than a mutation in one of the genes was moderate. But if one
of the three genes had a lower expression level because of the genetic background,
than the mutation was severe. If a gene has a higher expression level than the
mutation was mild.
To understand the mechanisms of background effects we have crossed the two worm
strains from England and Hawaii and let them have many offspring with different
genetic backgrounds. So, each offspring has a different genetic background. We then
knocked down different genes in this suite of different genetic backgrounds (called
recombinant inbred lines) and compared these to normal worms. The genes were
10 | Prof.dr J.E. Kammenga Hidden genetic variation
Figure 6. Effect of gene knock-downs in different genetic backgrounds. The four panels show a range of
different strains (vertical) and 6 chromosomes (horizontal). The above-left panel is the control treatment
where the strains have not been affected by a gene knock-down. The phenotype (fitness) shows a normal
variation across the strains. The other three panels show the same range of different backgrounds but here
they are affected by a gene knock-down (the red line). Depending on the position of the gene and the
genetic background, fitness varies
knocked down in Chr IV, II and X. We found that overall health depended on i) the
gene that was knocked-down, and ii) the genetic background in which the gene was
knocked-down[14] (Figure 6).
Opposite mutants
To gain un understanding of the background effects of mutations at the genome level
we created two different populations in C. elegans, these are the so-called “opposite”
mutants. The first population consists of the English background with small Hawaii
mutations (orange-blue worms) the other consists of the Hawaii background with
small English mutations (blue-orange worms) (Figure 7). This allows for studying the
effect of each mutation at each part of the genome for background effects. It should
be mentioned here that these populations are unique and do not exist for any other
species yet. So each strain is a sort of mutant.
Analysis of stress reactions in the worm has revealed some interesting aspects of
background interactions. We studied stress responses because these are determined
by the same pathways that are involved in human diseases. Heat-shock is a relevant
treatment in C. elegans because it induces genetic pathways which are associated with
developmental diseases in mammals (Figure 8).
Wageningen University & Research | 11
Figure 7. Two opposite mutant populations of
C. elegans. De figure shows the genomic
positions of the allelic markers (horizontal) and
the different individuals (vertical). Allelic
variants of Hawaii in blue and England in
orange. Thanks to A. Doroszuk, L.B. Snoek and
M. Sterken.
Figure 8. Exposure of C. elegans to abiotic stress factors like hypoxia, heat stress or oxidative stress induces
genes and pathways that underlie complex diseases in mammals, including humans [15]. Therefore,
studying these stress factor responses in C. elegans is relevant for understanding disease phenotypes.
12 | Prof.dr J.E. Kammenga Hidden genetic variation
Figure 9. Survival after heat-shock, measured in blue-orange worms,
orange-blue worms, orange and blue worms. The survival is determined by an
interaction between the introgression and the genetic background (ANOVA, p
< 0.01). Thanks to M. Sterken.
We exposed young worms to a heat-shock of 35°C for 4 hours after which we
recorded survival of the worms. We detected a position on chromosome IV that
controlled the heat-shock response. Selected individuals (orange worms with a bit of
blue; and blue worms with a bit of orange) were tested. Figure 9 shows there is
hardly any difference in survival at 20°C between blue worms, orange worms,
orange-blue worms and blue-orange worms. But after the heat-shock of 4 hours, we
recorded a survival of 50% for blue worms, approx.. 60% for orange worms, up to
80% for orange-blue worms, and 40% for blue-orange worms. In conclusion,
survivorship is determined by the interaction between the mutations and the
background.
It is evident that pathways cannot be disconnected from their genetic background.
Indeed, the mutation effects in pathways can be overshadowed. We took this a step
further and investigated the genetic mechanism underlying the background effect of
a mutation in a gene that is known to cause cancer (the let-60 oncogene) under
certain conditions. Over-activating the gene leads to clear swellings of the body of the
worm (Figure 10).
So the normal development is disrupted. Analogous mutations in mammals lead to
a disrupted cell division and onset of cancer formation[16]. In our research together
with Swiss partners[17] we introduced the activated oncogene into a large number
of different genetic backgrounds. These individuals developed a wide range of
external swellings, more as well as less than their parents (Figure 11).
Wageningen University & Research | 13
Figure 10. Activation of the oncogene let-60 in C.
elegans leads to developmental disruption which is
visible by external swellings of the worm. Picture by
T. Schmid.
Figure 11. Effect of genetic
background (C. elegans strains) on
the number of external swellings due
to the mutation in oncogene let-60.
Thanks to L.B. Snoek, T. Schmid
and A. Hajnal.
Many more than could be expected compared to the original mutant, a clear
background effect. We revealed a “modifier” background gene on chromosome I that
encodes for monoamine oxidase A (MAOA). The monoamine oxidase A catalyzes the
formation of 5-Hydroxyindoleacetic acid (5-HIAA). Worms activated for 5-HIAA
displayed increased number of swellings due to the oncogene than worms that did
not have an activated form of this gene. We then asked if this compound would affect
human cancer. We found that 5-Hydroxyindoleacetic acid inhibits the development
of colon cancer human cell lines (in prep.). So we found that for the oncogene on
chromosome IV there was a modifier gene on chromosome I.
14 | Prof.dr J.E. Kammenga Hidden genetic variation
These results all illustrate that the genetic background can have a surprising effect on
the impact of mutations. This may have consequences for the latest fancy tool in
genetics: genome editing; where very specific mutations are tailor made and
investigated for their phenotypic effects. For instance we can very precisely cut and
paste in a gene to make a worm glow like a light bulb or make it obese. But given
what we know about background effect on mutations, we should be cautious in our
interpretation and promises about this technique. At the moment we know very little
about the relation between genetic background and genome editing. We will be
testing the effect of genome editing in the worms that we have. More interestingly
perhaps is that we will introduce huge amounts of variation by not using two parents
but four, to increase diversity. In this case we sampled worms from different
locations like rotting apples and hogweed plants.
Genetic individuality: tailor made?
Why are these worm experiments so important? These experiments show that a
genomic change is not the cause of the phenotype but the results of the genomic
change PLUS the interaction between the genomic change and the background.
These results provide mechanistic insight and imply that the effect of each mutation
must be evaluated within the context of the individual: from recognition to
acknowledgement. This may ring a bell regarding personalized medicine, or in other
words, tailor made therapies and medication on the basis of the individual genomic
characteristics. But here we should tread cautiously. Even in case of a personal
passport of the genomic constitution of animals, humans or plants or crops perhaps
highlighting the type of mutations they carry. Simply because we do not know the
complex interactions between the mutation and the genetic background. A genetic
passport based on gene sequence is too simplistic. Clearly this goes beyond the
dominant or recessive character of a particular gene. But let’s be modest about our
promises and objectives. The publication of the human genome sequence[18] was
presented as the holy grail. By then, promises were made that the elucidation of the
human DNA-sequence would unlock the secrets for developing new medicine and
medication. Unfortunately we have to admit that these developments do not match
up to the promises made (NYT, 2010). Ten years after the presentation of the first
draft of the human genome, medicine has not matched up to the promises made.
Only recently have we made progress in applying gene therapies based on the
genome sequence. This means that we cannot make the step from single gene
mutation to medical treatment or, in case of plants, for instance, compactness in
Petunia. We should be more careful in making promises about societal relevance and
potential applications and try to understand the complex genetic interactions because
we are far from understanding this complexity yet. We have seen a huge variation
between different backgrounds within species, and perhaps we should be a bit more
Wageningen University & Research | 15
modest in conveying our message to the public. Editing humanity and promises
about the gene machine should be taken with a pinch of salt.
Only a few weeks ago this paper came out in Nature[19]. It emphasized that current
genomic insights fall short on the diversity and variation that we witness in human
populations. This is about the challenge of understanding genetic individuality. Let’s
hope we can provide a little bit of mechanistic insight into this pressing problem by
exploring the hidden genetic diversity in the worm.
Dear students
You have been a source of inspiration for my work. I regard myself a privileged
person to work amidst young, enthusiastic and intelligent people. From me it is
expected to supervise you in a professional way. This has been a challenge because
there is the risk of being your waiter rather than supervisor. In my opinion we ask
“Are you being served?” to often. We guide you through the lectures, the practical’s,
and tutorials. We work on assignments, design of experiments after which these need
to be analyzed and discussed. You receive a wide variety of support which often is
tailor made. All different kinds of services and products are at your disposal.
Examples are provided galore and you are allowed to rate everything, from whole
courses to individual teachers. These are typical characteristics of customers. In my
opinion you should also behave as investors. Now the balance has shifted a bit too
far to the customer side. As investor you struggle on the road to success, you expect
nothing and invest in yourself (Figure 12).
My role as waiter should be transformed into supervisor. It is not enough to teach
you how to design experimental setups, to conduct proper experimentation and how
to analyze the data and writing reports. To achieve this, I would like to paraphrase
Rikard Nordraak, the famous Norwegian composer. He said: to understand music
you need to go beyond music itself. This should apply to you: To understand science
you need to go beyond science itself. By this I mean that apart from all the skills,
expertise, knowledge and insights that we offer you, you need to doubt your results.
You need to question your own data and ask, apart from all proper scientific conduct,
whether it makes sense. You will not find any rules for this; we need to train you to
do this. This is important because it lays the foundation to the road of success. This is
my second message.
Beste scholieren
Ik kom regelmatig op basisscholen om kinderen het belang en de schoonheid van
wetenschap te laten zien. Dit vindt plaats ihkv het wetenschapsknooppunt was als
missie heeft om de nieuwsgierige en onderzoekende houding van kinderen en
(aankomende) leraren te bevorderen. Ik kom op diverse scholen en zie hoe kinderen
16 | Prof.dr J.E. Kammenga Hidden genetic variation
Figure 12. The attitude and behavior of students is shifted to the
customer side of the balance. More weight should be emphasized
on the role of personal investor
enorm enthousiast zijn en zich werkelijk vastbijten in de wetenschappelijke
voorbeelden die ze voorgelegd krijgen. Zo leg ik het verschil uit tussen goochelen,
toveren en wetenschap; en neem ik ze mee op een zoektocht naar de vraag hoe het
toch zou kunnen dat een schildpad 200 jaar wordt, je konijn maar 3 jaar en onze
worm maar 3 weken. En dit is dankbaar werk want ik krijg hele mooie tekeningen
van ze (Figure 13). Maar ik ben pas tevreden als ik bijna zeker weet dat ze ’s middags
naar huis gaan en voluit vertellen over hun speciale les.
Tegelijkertijd zie ik op die scholen ook een enorme diversiteit aan bevolkingsgroepen.
Allemaal zijn ze vol interesse en leergierigheid. Een eigenschap van veel kinderen
natuurlijk. Maar bij de studenten die naar Wageningen komen is deze etnische
diversiteit niet hoog. Er zijn weinig studenten bij met allochtone achtergrond. En die
mis ik. De medelanders. In een tijd waarin de kloof tussen verschillende
bevolkingsgroepen groter wordt en er minder ruimte is voor dialoog en begrip is het
essentieel dat de thema’s waar wij hier in Wageningen aan werken worden opgelost
door een verscheidenheid aan mensen uit diverse bevolkingsgroepen. Ja, degenen
met een andere immigratie achtergrond. Alleen door verbondenheid komen we
verder. Dit is mijn derde en laatste boodschap: een verbondenheid die moet leiden
tot toewijding en betrokkenheid binnen onze samenleving. Ik zie dit als een manier
om een meer coherente maatschappij te vormen waarbij allerlei groepen niet naast
elkaar maar met elkaar het hoofd bieden aan de huidige uitdagingen waar
Wageningen University en Research zich voor gesteld ziet. Ik heb hierover intussen
al contact opgenomen met de afdeling onderwijsbeleid van Wageningen University
om te zien hoe we dit vraagstuk op kunnen pakken.
Wageningen University & Research | 17
Figure 13. Enthusiastic drawing of C. elegans. Group 5.
Woord van dank
Hiermee kom ik aan het eind van mijn inaugurele rede. Dit is het moment om de
mensen te bedanken die het mogelijk hebben gemaakt dat ik hoogleraar ben
geworden. Jaap Bakker, mentor vanaf het eerste uur. Jij schonk me het vertrouwen en
gaf me de ruimte om dit te bereiken. Maar nooit zonder een kritische blik en
waardevolle tips en suggesties. Jaap, jouw visie op wetenschap en mensen is
ongeëvenaard en van grote betekenis geweest voor mij. Joost Riksen: ik heb dit niet
kunnen doen zonder jou. De wijze waarop jij het lab al jaren organiseert en je
uitstekende manier van praktische begeleiding van studenten en PhD’s vormen één
van de pijlers van de C. elegans groep. Je bent deskundig, stress bestendig en hebt een
groot verantwoordelijkheidsgevoel. Bedankt voor al die jaren dat ik met je mocht
samenwerken. Basten Snoek: wie anders is er in staat om op een heldere manier
grote hoeveelheden data te analyseren en dit terug te brengen tot iets wat iedereen
kan begrijpen en waar iedereen mee verder kan. Je bent een kei in het onderhouden
van contacten met andere collega’s en om met hun samen te werken op een
vruchtbare manier. Rita Volkers, dankzij jouw inzet hebben we goed inzicht
gekregen in de wilde isolaten van C. elegans. Mark Sterken; ik wil je danken voor je
enorme loyaliteit naar de leerstoelgroep en de wijze waarop je al die studenten hebt
begeleid die bij ons een thesis hebben gedaan.
18 | Prof.dr J.E. Kammenga Hidden genetic variation
begeleid die bij ons een thesis hebben gedaan. Daarnaast is jouw bijdrage aan het
onderzoek van groot belang geweest voor de lange termijn strategie van het C.
elegans onderzoek. De stafleden van de leerstoelgroep Nematologie, Aska Goverse,
Geert Smant, Hans Helder en Arjen Schots wil ik bedanken voor hun support en
enorme collegialiteit die van belang is om onze gezamenlijke doelen na te streven. Ik
bedank all aio’s, postdocs en studenten die een enorme bijdrage hebben geleverd aan
het C. elegans onderzoek en alle collega’s met wie ik gezamenlijk onderwijs geef. Ik
wil graag de Rector Magnificus en leden van de benoemingsadvies commissie
bedanken voor het door hun in mij gestelde vertrouwen. Lisette Groeneveld en
Christel van Geelen dank ik voor hun bereidheid om altijd klaar te staan om mijn
haastklussen goed af te handelen en voor het scherp in de gaten houden van
administratieve zaken omtrent de projecten en het onderwijs. Alle leden van de
leerstoelgroep Nematologie wil ik bedanken voor de enorm goede sfeer. Dit maakt
het een hele prettige werkomgeving.
En dan nu een dankwoord voor mijn naasten. Voor mijn ouders omdat ze mij al heel
vroeg hebben geleerd om kansen te grijpen en om te laten beseffen dat je jezelf moet
blijven ontwikkelen. Renate, Eline en Rosanne, omdat jullie er altijd voor zorgen dat
naar huis gaan “thuis komen” betekent en dat er niets gaat boven “home sweet
home”. Eline en Rosanne, jullie zijn twee fantastische dochters. Renate, jou wil ik
extra bedanken voor je begrip, liefde en alle steun door de jaren heen. Jouw
relativeringsvermogen, warmte en humor maakten het mede mogelijk dat ik hier
nu sta.
Ik heb gezegd
Wageningen University & Research | 19
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20 | Prof.dr J.E. Kammenga Hidden genetic variation
Prof.dr J.E. Kammenga
There is general consensus that gene mutations are considered
as separate entities. But their phenotypes do not result from
isolated mutations but from the interaction between the
mutations and the genetic individuality. At the moment we do not
understand this hidden genetic variation and are surprised by the
intrinsic complexity of individual plants and animals. I draw upon
the importance of genetic individuality for the expression of
mutations and explain how we can understand the individual
complexity of gene mutations.
isbn
978-94-6343-135-4